Abstract

The activity of the hypothalamus-pituitary-thyroid (HPT) axis is inhibited by energy deficit, by acute or chronic stress, but activated by cold exposure or exercise. Because stress curtails acute cold induced activation of HPT, we evaluated the effect of chronic stress on HPT axis response to voluntary exercise, a persistent energy-demanding situation. Adult male and female Wistar rats were exposed to restraint stress, 30 min/day for 2 weeks, or to isolation (Iso) [post-natal day [PND] 30–63]. Exercise was performed (7 p.m.−7 a.m.) in a running wheel, sedentary controls stayed in individual cages (Sed); at 7 a.m. they were housed with their cage mate or individually (Iso); food intake by the exercised group was measured day and night to pair-fed Sed. At sacrifice, hormones, mRNA levels and tissue weights were quantified. Control or restrained adult rats had access to running wheel daily for 2 weeks. Compared to C, exercise decreased white adipose tissue (WAT) mass in females and males, increased hypothalamic paraventricular nucleus (PVN)-Trh expression in males proportionally to exercise performed, and increased TSH and T4 serum concentration in females. These changes were not detected in restrained groups. Starting at PND 63 control (2/cage) and isolated (1/cage) rats either exercised on 10 alternated nights or were sedentary. In control male animals, compared to Sed rats, exercise did not decrease WAT mass, nor changed HPT axis activity, but increased Pomc and deiodinase 2 (Dio2) expression in mediobasal hypothalamus (MBH), adrenergic receptor β3 and uncoupling protein-1 in brown adipose tissue. In control female animals, exercise decreased WAT mass, increased Pomc, Dio2, and Trhde expression in MBH, and TSH serum concentration. Iso females had lower TSH and T4 serum concentration, Dio2 and Trhde expression in MBH than controls. The stress response was higher in isolated males than females, but in males it did not alter the effects of exercise, in contrast to isolated females that had a blunted response to exercise compared to controls. In conclusion, chronic stress interferes with metabolic effects produced by exercise, such as loss of WAT mass, coincident with dampening of HPT activity.

Highlights

  • Physical activity and food intake are the two most important controllable variable in setting body weight

  • Using this paradigm we previously demonstrated that compared to sedentary animals exercised rats decrease their food intake and mass of white adipose tissue (WAT), and diminish the parameters that reflect HPT axis activity; if values are compared to a pair-fed group there is still a strong decrease in WAT mass, but paraventricular nucleus (PVN) Trh expression, TSH and T3 serum concentrations are higher and proportional to the loss of WAT mass [19]

  • We studied the response of the HPT and HPA axes and WAT depots to voluntary wheel running in male and female rats submitted to two types of chronic stress: (a) 2 weeks of intermittent restraint in adult animals, and (b) isolation caused by keeping rats in individual housing since puberty

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Summary

Introduction

Physical activity and food intake are the two most important controllable variable in setting body weight. Tissue levels of thyroid hormones are regulated by the activity of the hypothalamic-pituitary-thyroid (HPT) axis, and at target cells by transporters, deiodinases, and membrane or intracellular TH receptors, the latter acting as transcription factors [1, 7,8,9]. The HPT axis is subject to multifactorial regulation, initiating with neurons of the hypothalamic paraventricular nucleus (PVN) that synthesize thyrotropin releasing hormone (TRH) and release it in the median eminence, in the vicinity of portal vessels and β2-tanycytes. These neurons receive multiple afferents from the arcuate nucleus and other brain areas that convey information of environmental, nutritional and metabolic status [10, 11]. T3 is the active hormone at transcriptional level and responsible for feedback inhibition on TRH and TSH synthesis [7, 14, 15]

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